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Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination
Author(s) -
Bernard Frédéric,
MoreauFauvarque Caroline,
HeitzMarchaland Céline,
Zagar Yvrick,
Dumas Laura,
Fouquet Stéphane,
Lee Xinhua,
Shao Zhaohui,
Mi Sha,
Chédotal Alain
Publication year - 2012
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22378
Subject(s) - semaphorin , plexin , oligodendrocyte , axon guidance , biology , neuroscience , transmembrane protein , myelin , myelin basic protein , microbiology and biotechnology , axon , central nervous system , receptor , genetics
Myelination is regulated by extracellular proteins, which control interactions between oligodendrocytes and axons. Semaphorins are repulsive axon guidance molecules, which control the migration of oligodendrocyte precursors during normal development and possibly in demyelinating diseases. We show here that the transmembrane semaphorin 6A (Sema6A) is highly expressed by myelinating oligodendrocytes in the postnatal mouse brain. In adult mice, Sema6A expression is upregulated in demyelinating lesions in cuprizone‐treated mice. The analysis of the optic nerve and anterior commissure of Sema6A‐deficient mice revealed a marked delay of oligodendrocyte differentiation. Accordingly, the development of the nodes of Ranvier is also transiently delayed. We also observed an arrest in the in vitro differentiation of purified oligodendrocytes lacking Sema6A, with a reduction of the expression level of Myelin Basic Protein. Their morphology is also abnormal, with less complex and ramified processes than wild‐type oligodendrocytes. In myelinating co‐cultures of dorsal root ganglion neurons and purified oligodendrocytes we found that myelination is perturbed in absence of Sema6A. These results suggest that Sema6A might have a role in myelination by controlling oligodendrocyte differentiation. © 2012 Wiley Periodicals, Inc